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 Research & Giving News Article  Stress Response Variability Low levels of “Neuropeptide Y” are associated with high levels of anxiety “Stress response is an important variable in vulnerability to alcohol dependence and other addictions, as well as other psychiatric disorders,” noted Ting-Kai Li, M.D., Director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), which led the study. “This finding could help us understand individuals’ initial vulnerability to these disorders.” Mutant genes for Neuropeptide Y, a signaling protein David Goldman, M.D., chief of the NIAAA Laboratory of Neurogenetics, and colleagues at NIAAA and seven other institutions identified gene variants that affect the expression of a signaling molecule called neuropeptide Y (NPY). Found in brain and many other tissues, NPY regulates diverse functions, including appetite, weight and emotional responses. “NPY is induced by stress and its release reduces anxiety,” said Dr. Goldman. “Previous studies have shown that genetic factors play an important role in mood and anxiety disorders. In this study, we sought to determine if genetic variants of NPY might contribute to the maladaptive stress responses that often underlie these disorders.” A report of the findings appeared online in the journal Nature on April 2. Among the authors were Ahmad R. Hariri, Ph.D., an assistant professor at the University of Pittsburgh and a 2003 NARSAD Young Investigator, and Jon-Kar Zubieta, M.D., Ph.D., an associate professor at the University of Michigan and a NARSAD 1998 Young Investigator and 2002 and 2004 Independent Investigator. The research team’s analyses of human tissue samples identified several NPY gene variants. They determined that these mutant genes cause a range of different effects including altered levels of NPY in brain and other tissues, and differences in emotion and emotion-induced responses of the brain. Impact of the mutant gene on stress and emotion Importantly, the researchers evaluated how the variant genes caused changes that affected brain responses to stress and emotion. Using functional brain imaging, they found that people who had the particular variation that yielded the lowest level of NPY reacted with heightened emotion to images of threatening facial expressions. “Metabolic activity in brain regions involved in emotional processing increased when these individuals were presented with the threatening images,” explained Dr. Goldman. In another brain imaging experiment, people with the low-level NPY variant were found to have a diminished ability to tolerate moderate levels of sustained muscular pain. Previous studies had shown that NPY’s behavioral effects are mediated through interactions with opioid compounds produced by the body to help suppress pain, stress, and anxiety. “As shown by brain imaging of opioid function, these individuals released less opioid neurotransmitter in response to muscle discomfort than did individuals with higher levels of NPY,” said Dr. Goldman. “Their emotional response to pain was also higher, showing the close tie between emotionality and resilience to pain and other negative stimuli.” In a preliminary finding, the low-level NPY gene variant was found to be more common than other variants among a small sample of individuals with anxiety disorders. The researchers also found that low-level NPY expression was linked to high levels of trait anxiety. “Trait anxiety is an indication of an individual’s level of emotionality or worry under ordinary circumstances,” said Dr. Goldman. The researchers conclude that these converging findings are consistent with NPY’s role as an anxiety-reducing peptide and help explain variations among individuals in resiliency to stress. “This inherited functional variation could open up new avenues of research for other human characteristics, such as appetite and metabolism, which are also modulated by NPY,” said Dr. Goldman. |
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